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次氯酸产生电化学绷带在小鼠多微生物伤口感染中具有活性。

HOCl-producing electrochemical bandage is active in murine polymicrobial wound infection.

机构信息

Division of Clinical Microbiology, Mayo Clinic, Rochester, Minnesota, USA.

The Gene and Linda Voiland School of Chemical Engineering and Bioengineering, Washington State University, Pullman, Washington, USA.

出版信息

Microbiol Spectr. 2024 Oct 3;12(10):e0062624. doi: 10.1128/spectrum.00626-24. Epub 2024 Aug 20.

Abstract

UNLABELLED

Wound infections, exacerbated by the prevalence of antibiotic-resistant bacterial pathogens, necessitate innovative antimicrobial approaches. Polymicrobial infections, often involving and methicillin-resistant (MRSA), present challenges due to biofilm formation and antibiotic resistance. Hypochlorous acid (HOCl), a potent antimicrobial agent, holds promise as an alternative therapy. An electrochemical bandage (e-bandage) that generates HOCl via precise polarization controlled by a miniaturized potentiostat was evaluated for the treatment of murine wound biofilm infections containing both with "difficult-to-treat" resistance and MRSA. Previously, HOCl-producing e-bandage was shown to reduce murine wound biofilms containing alone. Here, in 5-mm excisional skin wounds containing 48-h biofilms comprising MRSA and combined, polarized e-bandage treatment reduced MRSA by 1.1 log CFU/g ( = 0.026) vs non-polarized e-bandage treatment (no HOCl production), and 1.4 log CFU/g (0.0015) vs Tegaderm only controls; was similarly reduced by 1.6 log CFU/g ( = 0.0032) and 1.6 log CFU/g ( = 0.0015), respectively. For wounds infected with MRSA alone, polarized e-bandage treatment reduced bacterial load by 1.1 log CFU/g ( = 0.0048) and 1.3 log CFU/g ( = 0.0048) compared with non-polarized e-bandage and Tegaderm only, respectively. The e-bandage treatment did not negatively impact wound healing or cause tissue toxicity. The addition of systemic antibiotics did not enhance the antimicrobial efficacy of e-bandages. This study provides additional evidence for the HOCl-producing e-bandage as a novel antimicrobial strategy for managing wound infections, including in the context of antibiotic resistance and polymicrobial infections.

IMPORTANCE

New approaches are needed to combat the rise of antimicrobial-resistant infections. The HOCl-producing electrochemical bandage (e-bandage) leverages generation of HOCl, a natural biocide, for broad-spectrum killing of wound pathogens. Unlike traditional therapies that may exhibit limited activity against biofilms and antimicrobial-resistant organisms, the e-bandage offers a potent, standalone solution that does not contribute to further resistance or require adjunctive antibiotic therapy. Here, we show the ability of the e-bandage to address polymicrobial infection by antimicrobial resistant clinical isolates of and , two commonly isolated, co-infecting wound pathogens. Effectiveness of the HOCl-producing e-bandage in reducing pathogen load while minimizing tissue toxicity and avoiding the need for systemic antibiotics underscores its potential as a tool in managing complex wound infections.

摘要

目的

创伤感染普遍存在抗生素耐药的细菌病原体,需要创新的抗菌方法。混合感染,常涉及金黄色葡萄球菌和耐甲氧西林金黄色葡萄球菌(MRSA),由于生物膜形成和抗生素耐药性而带来挑战。次氯酸(HOCl)作为一种有效的抗菌剂,具有替代治疗的潜力。一种通过小型电化学工作站控制精确极化产生 HOCl 的电化学绷带(e-绷带),用于治疗含有耐“难治疗”的金黄色葡萄球菌和 MRSA 的小鼠创伤生物膜感染。先前,产生 HOCl 的 e-绷带已显示可减少单独含有金黄色葡萄球菌的小鼠创伤生物膜。在这里,在含有 48 小时生物膜的 5mm 切除皮肤伤口中,MRSA 和金黄色葡萄球菌的组合,经极化 e-绷带治疗后,与非极化 e-绷带治疗(无 HOCl 产生)相比,MRSA 减少了 1.1log CFU/g( = 0.026),与 Tegaderm 单独对照相比减少了 1.4log CFU/g(0.0015);金黄色葡萄球菌也分别减少了 1.6log CFU/g( = 0.0032)和 1.6log CFU/g( = 0.0015)。对于仅感染 MRSA 的伤口,与非极化 e-绷带和仅 Tegaderm 相比,极化 e-绷带治疗分别使细菌负荷减少了 1.1log CFU/g( = 0.0048)和 1.3log CFU/g( = 0.0048)。e-绷带治疗不会对伤口愈合产生负面影响,也不会引起组织毒性。全身性抗生素的添加并没有增强 e-绷带的抗菌功效。本研究为 HOCl 产生的 e-绷带作为一种治疗伤口感染的新型抗菌策略提供了更多证据,包括在抗生素耐药性和混合感染的情况下。

意义

需要新的方法来对抗抗生素耐药感染的增加。产生次氯酸的电化学绷带(e-绷带)利用次氯酸(HOCl)的产生,HOCl 是一种天然的杀菌剂,可广谱杀灭伤口病原体。与传统疗法相比,传统疗法可能对生物膜和抗微生物药物耐药的生物体表现出有限的活性,e-绷带提供了一种有效的、独立的解决方案,不会导致进一步的耐药性或需要辅助抗生素治疗。在这里,我们展示了 e-绷带通过抗菌药物耐药的临床分离金黄色葡萄球菌和耐甲氧西林金黄色葡萄球菌(MRSA)两种常见的混合感染伤口病原体来解决混合感染的能力。HOCl 产生的 e-绷带在减少病原体负荷的同时最大限度地减少组织毒性并避免使用全身性抗生素的能力,突显了其作为管理复杂伤口感染的工具的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fc3/11448380/0e015d04fc66/spectrum.00626-24.f001.jpg

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